Rate of Evolution in Brain-Expressed Genes in Humans and Other Primates

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Abstract
Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM) and then conducted three-way comparisons among (i) mouse, OWM, and human, and (ii) OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse), a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal) in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i) faster evolution in gene expression, and (ii) a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed. Whether comparing morphology or cognitive ability, it is clear that the human brain has evolved rapidly relative to that of other primates. But the extent to which genes expressed in the brain also reflect this overall pattern is unclear. To address this question, it's necessary to measure any variations in the DNA sequences of these genes between human and chimpanzee. And, to do this as accurately as possible, it's also important to require an appropriate reference group to act as a benchmark against which the differences can be measured. We therefore compared publicly available genomic sequences of chimps and humans with complementary DNA sequences of several thousand genes expressed in the brain of another closely related primate—the macaque, an Old World monkey—as well as the more distantly related mouse. Our analyses of the rates of protein evolution in these species suggest that genes expressed in the human brain have in fact slowed down in their evolution since the split between human and chimpanzee, contrary to some previously published reports. We suggest that advanced brains are driven primarily by the increasing complexity in the network of gene interactions. As a result, brain-expressed genes are constrained in their sequence evolution, although their expression levels may change rapidly.